Single-dose methamphetamine administration impairs ORM retrieval in mice via excessive DA-mediated inhibition of PrLGlu activity.

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

BMSC loaded photo-crosslinked hyaluronic acid/collagen hydrogel incorporating FG4592 for enhanced cell proliferation and nucleus pulposus differentiation.

Intervertebral disc degeneration arises from damage or degeneration of the nucleus pulposus (NP). In this study, we developed a photo-crosslinkable hydrogel incorporating FG4592 to support the growth and differentiation of bone-marrow-derived mesenchymal stem cells (BMSC). Initially, hyaluronic acid was modified with tyramine and combined with collagen to introduce riboflavin as a photo-crosslinker. This hydrogel transitioned from liquid to gel upon exposure to blue light in 3 min. The results showed that the hydrogel was biodegradable and had mechanical properties comparable to those of human NP tissues. Scanning electron microscopy after BMSC seeding in the hydrogel revealed an even distribution, and cells adhered to the collagen fibers in the hydrogel with minimal cell mortality. The effect of FG4592 on BMSC proliferation and differentiation was examined, revealing the capability of FG4592 to promote BMSC proliferation and direct differentiation resembling human NP cells. After cultivating BMSCs in the photo-crosslinked hydrogel, there was an upregulation in the expression of glycosaminoglycans, aggrecan, type II collagen, and keratin 19 proteins. Cross-species analyses of rat and human BMSCs revealed consistent results. For potential clinical applications, BMSC loaded with photo-crosslinked hydrogels can be injected into damaged intervertebral disc to facilitate NP regeneration.

The Association Between Antidepressant Use and Drug-Induced Liver Injury: A Nationwide, Population-Based Case-Control Study in Taiwan.

BACKGROUND AND OBJECTIVE: The complex risk factors of liver injury have prevented the establishment of causal relationships. This study aimed to explore the effects of antidepressant class, cumulative days of medication exposure, presence of comorbidities, and the use of confounding drugs on the risk of antidepressant-induced liver injury. METHODS: The population-based case-control study sample included individuals registered on the Taiwan National Health Insurance Database between 2000 and 2018. Hospitalized patients with suspected drug-induced liver injury were considered as cases, while control subjects were matched 1:1 by age, gender, and index date (the first observed diagnosis of liver injury). Multivariable regression models were performed to evaluate the association between antidepressants and liver injury. RESULTS: The findings showed that antidepressant users exhibited a higher risk of liver injury (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.12-1.20), particularly those prescribed non-selective serotonin reuptake inhibitors (NSRIs; aOR 1.05; 95% CI 1.01-1.10), selective serotonin reuptake inhibitors (SSRIs; aOR 1.22; 95% CI 1.16-1.29), serotonin-norepinephrine reuptake inhibitors (SNRIs; aOR 1.18; 95% CI 1.13-1.24), and others (aOR 1.27; 95% CI 1.14-1.42). Moreover, cases exhibited a more significant proportion of antidepressant usage and longer durations of treatment compared with controls. The risk of liver injury was higher in the first 30 days of use across all classes of antidepressants (aOR 1.24; 95% CI 1.18-1.29). CONCLUSION: SSRIs or SNRIs are commonly used to treat depression and other psychological disorders, and consideration of their potential effects on the liver is essential.

Sex differences of signal complexity at resting-state functional magnetic resonance imaging and their associations with the estrogen-signaling pathway in the brain.

Sex differences in the brain have been widely reported and may hold the key to elucidating sex differences in many medical conditions and drug response. However, the molecular correlates of these sex differences in structural and functional brain measures in the human brain remain unclear. Herein, we used sample entropy (SampEn) to quantify the signal complexity of resting-state functional magnetic resonance imaging (rsfMRI) in a large neuroimaging cohort (N = 1,642). The frontoparietal control network and the cingulo-opercular network had high signal complexity while the cerebellar and sensory motor networks had low signal complexity in both men and women. Compared with those in male brains, we found greater signal complexity in all functional brain networks in female brains with the default mode network exhibiting the largest sex difference. Using the gene expression data in brain tissues, we identified genes that were significantly associated with sex differences in brain signal complexity. The significant genes were enriched in the gene sets that were differentially expressed between the brain cortex and other tissues, the estrogen-signaling pathway, and the biological function of neural plasticity. In particular, the G-protein-coupled estrogen receptor 1 gene in the estrogen-signaling pathway was expressed more in brain regions with greater sex differences in SampEn. In conclusion, greater complexity in female brains may reflect the interactions between sex hormone fluctuations and neuromodulation of estrogen in women. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09954-y.

Compact efficient high-power continuous-wave Nd:YVO4/KGW/LBO Raman lasers for selectable wavelengths within 559-603†nm.

Compact efficient high-power continuous-wave Nd:YVO4 Raman lasers for selectable wavelengths within 559-603 nm are achieved by using KGW crystal for intracavity stimulated Raman scattering (SRS) and lithium triborate (LBO) crystal for intracavity sum frequency generation (SFG) and second harmonic generation (SHG). The LBO crystal with the cut angle in the XY plane for the type-I phase matching is used to perform intracavity SHG or SFG. Experimental results reveal that the participated Stokes lines include the internal vibration mode at 901 cm-1, the external vibrational mode at 209 cm-1, and the combination mode of the 901 cm-1 and 209 cm-1 Raman shifts. By tuning LBO temperature for attaining the maximum output power, the output spectrum reveals the triple peaks of 588.7, 595.7, and 603.1 nm with the intensity ratio of 10:4:1. Under this circumstance, the output power can reach the highest value of 10.8 W at a pump power of 40 W. Furthermore, the output spectrum can be simply concentrated on the single peaks among 588.7 (orange), 565.7 (yellow), and 559.1 nm (lime) by tuning LBO temperature to fulfill the selection of the critical phase matching. The output powers at a pump power of 40 W can be up to 8.0, 6.1, and 9.8 W for the single-peak emission at 588.7, 565.7, and 559.1 nm, respectively. Finally, a dual-peak emission of 565.7 and 572.3 nm with total output power of 5.2 W can be generated by tuning LBO temperature to match the SFG for 572.3 nm.

Highly efficient continuous-wave solid-state Raman crystal lasers at 555 and 559†nm.

High-power efficient continuous-wave Nd:YVO4/KGW Raman lasers at 555 and 559 nm are achieved by using a double-sided dichroic coating output coupler to improve the resonance quality factor. The Np-cut potassium gadolinium tungstate (KGW) is used to generate the Stokes waves at 1159 and 1177 nm by placing the polarization of the1064 nm fundamental wave parallel to the Ng and Nm axes, respectively. The lithium triborate (LBO) crystal with the cut angle in the XY plane for the type-I phase matching is used to perform the intracavity sum frequency generation for yielding the green light at 555 nm and the lime light at 559 nm at the optimal phase matching temperature. Experimental results were systematically accomplished to comprehend the optimal cavity length for the conversion efficiency. Under the optimal cavity length, the output powers can reach 6.6 and 6.3 W at a pump power of 22 W for the wavelengths of 555 and 559 nm, respectively. The conversion efficiencies can be up to 30% and 28.6% for 555 and 559 nm, respectively.

How to Prevent Nerve Root Injury in Uniportal Full Endoscopic Lumbar Fusion Surgery? Insights from a Cadaveric Anatomical Study with Simulation Surgery.

STUDY DESIGN: The study included two fresh-frozen cadavers. OBJECTIVE: To elucidate the positional relationship between surgical instruments and nerve roots during full endoscopic facet-sparing (FE fs-TLIF) and facet-resecting (FE fr-TLIF) lumbar interbody fusion and propose safe instrumentation insertion procedures and recommend cage glider designs aimed at protecting nerve roots. SUMMARY OF BACKGROUND DATA: Endoscopic surgical techniques are increasingly used for minimally invasive lumbar fusion surgery with FE fr-TLIF and FE fs-TLIF being common approaches. However, the risk of nerve root injury remains a significant concern during these procedures. METHODS: Eight experienced endoscopic spine surgeons performed uniportal FE fr-TLIF and FE fs-TLIF on cadaveric lumbar spines, totaling 16 surgeries. Post-operation, soft tissues were removed to assess the positional relationship between the cage entry point and nerve roots. Distances between the cage entry point, traversing nerve root, and exiting nerve root were measured. Safe instrumentation design and insertion procedures were determined. RESULTS: In FE fr-TLIF, the mean distance between the cage entry point and traversing nerve root was significantly shorter compared to FE fs-TLIF (3.30±1.35 mm vs. 8.58±2.47 mm, respectively; P<0.0001). Conversely, the mean distance between the cage entry point and the exiting nerve root was significantly shorter in FE fs-TLIF compared to FE fr-TLIF (3.73±1.97 mm vs. 6.90±1.36 mm, respectively; P<0.0001). For FE fr-TLIF, prioritizing the protection of the traversing root using a two-bevel tip cage glider was crucial. In contrast, for FE fs-TLIF, a single-bevel tip cage glider placed in the caudal location was recommended. CONCLUSION: This study elucidates the anatomical relationship between cage entry points and nerve roots in uniportal endoscopic lumbar fusion surgery. Protection strategies should prioritize the traversing root in FE fr-TLIF and the exiting root in FE fs-TLIF, with corresponding variations in surgical techniques. LEVEL OF EVIDENCE: V.

Amphiphilic NLC-Gel formulation loaded with Sebacoyl dinalbuphine ester and Nalbuphine for localized postoperative pain management.

Opioids are powerful analgesics; however, their significant systemic adverse effects and the need for frequent administration restrict their use. Nalbuphine (NA) is a κ-agonist narcotic with limited adverse effects, but needs to be frequently administrated due to its short elimination half-life. Whereas sebacoyl dinalbuphine ester (SDE) is a NA prodrug, which can effectively prolong the analgesic effect, but lacks immediate pain relief. Therefore, in this study, a rapid and sustained local delivery formulation to introduce NA and SDE directly into surgical sites was developed. An amphiphilic nanostructured lipid carrier (NLC) poloxamer 407 (P407) gel (NLC-Gel) was developed to permit concurrent delivery of hydrophobic SDE from the NLC core and hydrophilic NA from P407, offering a dual rapid and prolonged analgesic effect. Benefiting from the thermal-sensitive characteristic of P407, the formulation can be injected in liquid phase and instantly transit into gel at wound site. NLC-Gel properties, including particle size, drug release, rheology, and stability, were assessed. In vivo evaluation using a rat spinal surgery model highlighted the effect of the formulation through pain behavior test and hematology analysis. NLC-Gels demonstrated an analgesic effect comparable with that of commercial intramuscular injected SDE formulation (IM SDE), with only 15 % of the drug dosage. The inclusion of supplemental NA in the exterior gel (PA12-Gel + NA) provided rapid drug onset owing to swift NA dispersion, addressing acute pain within hours along with prolonged analgesic effects. Our findings suggest that this amphiphilic formulation significantly enhanced postoperative pain management in terms of safety and efficacy.

Investigating causal relationships between extensive peripheral immune cell phenotypes and preeclampsia: A bi-directional Mendelian randomization analysis.

PROBLEM: Preeclampsia, a multifaceted condition during pregnancy characterized by hypertension and organ dysfunction, poses significant risks to both maternal and fetal health. This study aims to investigate the bidirectional causal relationship between peripheral immune cell phenotypes and preeclampsia using a two-sample Mendelian randomization (MR) approach. METHOD OF STUDY: Genetic data from two sizable cohorts were utilized: 3757 individuals from Sardinia, providing information on 731 immune traits, and 200 929 Finnish adult females, encompassing 6663 preeclampsia cases. Single-nucleotide polymorphisms served as instrumental variables. The MR analyses employed the inverse variance-weighted (IVW) method as the primary tool, supplemented by MR-Egger, weighted median, and weighted mode methods to enhance reliability and address potential heterogeneity and horizontal pleiotropy. RESULTS: Among the 731 immune cell phenotypes studied, 18 displayed a suggestive positive association (IVW p < .05) with heightened preeclampsia risk, while 20 exhibited a suggestive negative association linked to reduced risk. Following false discovery rate (FDR) adjustment, four immune phenotypes showed significant associations with decreased preeclampsia risk: CD27 on CD24+ CD27+ B cells (B-cell panel) (odds ratio [OR] = 0.927, PFDR = 0.061), CD33+ HLA DR+ CD14- absolute count (OR = 0.963, PFDR = 0.061), CD80 on plasmacytoid dendritic cells (OR = 0.923, PFDR = 0.061); and CD80 on CD62L+ plasmacytoid dendritic cells (OR = 0.923, PFDR = 0.061). In the reverse-direction MR analysis, no significant causal effects of preeclampsia on immune cell phenotypes were observed. CONCLUSIONS: This study provides quantifiable evidence linking specific immune cell phenotypes to the risk of developing preeclampsia. This novel understanding of the immunological aspects underlying preeclampsia's pathogenesis could lead to innovative therapeutic strategies centered on immune modulation.

Risk of sleep disorders in patients with pneumoconiosis: a retrospective cohort study.

BACKGROUND: Pneumoconiosis is associated with pulmonary and cardiovascular diseases; however, the link between pneumoconiosis and sleep disorders is not well understood. This study aimed to investigate the connection between pneumoconiosis and subsequent risk of sleep disorders. METHODS: This population-based retrospective cohort study used data from the National Health Insurance database in Taiwan. The pneumoconiosis cohort consisted of 13,329 patients newly diagnosed between 2000 and 2015. The comparison group included 53,316 age-, sex-, and diagnosis date-matched individuals without pneumoconiosis. The development of sleep disorders was monitored until the end of 2018. Cox proportional hazard regression models were used for risk assessment. RESULTS: The incidence of sleep disorders was 1.31 times higher in the pneumoconiosis cohort than in the comparison cohort (22.8 vs. 16.2 per 1000 person-years). After controlling for age, sex, comorbidity, and medication, the adjusted hazard ratio (aHR) was 1.24 (95% confidence interval [CI] = 1.17-1.32). Stratified analyses by age group, sex, and comorbidity status showed significant associations between pneumoconiosis and sleep disorders (aHRs, 1.19-1.64). In addition, patients with pneumoconiosis had a significantly increased risk of developing sleep apnea (aHR = 1.71, 95% CI = 1.31-2.22). CONCLUSION: This study demonstrates that patients with pneumoconiosis are at a higher risk of developing sleep disorders and sleep apnea. Healthcare professionals should pay close attention to sleep quality and disturbances in patients with pneumoconiosis.

A missense mutation in human INSC causes peripheral neuropathy.

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.

The effect of colchicine on cancer risk in patients with immune-mediated inflammatory diseases: a time-dependent study based on the Taiwan's National Health Insurance Research Database.

BACKGROUND: To determine the effect of colchicine on cancer risk in patients with the immune-mediated inflammatory diseases (IMIDs)-related to colchicine use. METHODS: This is a time-dependent propensity-matched general population study based on the National Health Insurance Research Database (NHIRD) of Taiwan. We identified the IMIDs patients (n = 111,644) newly diagnosed between 2000 and 2012 based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-274,712, 135, 136.1, 279.49, 518.3, 287.0, 696.0, 696.1, 696.8, 420, 429.4, 710.0, 710.1, 710.3, 710.4, 714.0, 720, 55.0, 55.1, 55.9, 556. INCLUSION CRITERIA: aged ≧ 20 years, if a patient had at least these disease diagnosis requirements within 1 year of follow-up, and, these patients had at least two outpatient visits or an inpatient visit. After propensity-matched according to age, sex, comorbidities, medications and index date, the IMIDs patients enter into colchicine users (N = 16,026) and colchicine nonusers (N = 16,026). Furthermore, time-dependent Cox models were used to analyze cancer risk in propensity-matched colchicine users compared with the nonusers. The cumulative cancer incidence was analyzed using Cox proportional regression analysis. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (95% CIs) for cancer after adjusting for sex, age, comorbidities, and use of medicine including acetylcysteine, medication for smoking cessation such as nicotine replacement medicines (the nicotine patch) and pill medicines (varenicline), anti-inflammatory drugs and immunosuppressant drugs. RESULTS: Comparing the colchicine nonusers, all cancer risk were mildly attenuated, the (aHR (95% CI)) of all cancer is (0.84 (0.55, 0.99)). Meanwhile, the colchicine users were associated with the lower incidence of the colorectal cancer, the (aHRs (95% CI)) is (0.22 (0.19, 0.89)). Those aged < 65 years and male/female having the colchicine users were associated with lower risk the colorectal cancer also. Moreover, the colchicine > 20 days use with the lower aHR for colorectal cancer. CONCLUSION: Colchicine was associated with the lower aHR of the all cancer and colorectal cancer formation in patients with the IMIDs.

Inhaled anesthesia associated with reduced mortality in patients with stage III breast cancer: A population-based study.

BACKGROUND: Patients diagnosed with stage III breast cancer often undergo surgery, radiation therapy, and chemotherapy as part of their treatment. The choice of anesthesia technique during surgery has been a subject of interest due to its potential association with immune changes and prognosis. In this study, we aimed to compare the mortality rates between stage III breast cancer patients undergoing surgery with propofol-based intravenous general anesthesia and those receiving inhaled anesthetics. METHODS: Using data from Taiwan's National Health Insurance Research Database and Taiwan Cancer Registry, we identified a cohort of 10,896 stage III breast cancer patients. Among them, 1,506 received propofol-based intravenous anesthetic maintenance, while 9,390 received inhaled anesthetic maintenance. To ensure comparability between the two groups, we performed propensity-score matching. RESULTS: Our findings revealed a significantly lower mortality rate in patients who received inhaled anesthetics compared to those who received propofol-based intravenous anesthesia. Sensitivity analysis further confirmed the robustness of our results. CONCLUSIONS: This study suggests that inhaled anesthesia technique is associated with a lower mortality rate in clinical stage III breast cancer. Further research is needed to validate and expand upon these results.

Association Between Use of Sodium-Glucose Cotransporter-2 Inhibitors or Angiotensin Receptor-Neprilysin Inhibitor and the Risk of Atherosclerotic Cardiovascular Disease With Coexisting Diabetes and Heart Failure.

PURPOSE: This study was to investigate the association between the use of Sodium-glucose Cotransporter-2 inhibitors (SGLT2i) or angiotensin receptor-neprilysin inhibitor (ARNI; ie, Sacubitril + valsartan, Product name ENTRESTO) and the risk of atherosclerotic cardiovascular disease (ASCVD) in patients with coexisting diabetes and heart failure. Specifically, the study compared outcomes between patients using SGLT2i or valsartan + sacubitril and those not using these medications. METHODS: This study utilized data from the National Health Insurance Research Database (NHIRD) from 2017 to 2018. The case group consisted of 8691 patients with coexisting diabetes and heart failure who did not use SGLT2i or Entresto, while the control group consisted of 8691 patients with coexisting diabetes and heart failure who used SGLT2i or Entresto. The primary outcome was ASCVD, including a composite of cardiovascular death and hospitalization for worsening heart failure. Secondary outcomes included all-cause death, cause of cardiovascular death, and recurrence of heart failure, non-fatal myocardial infarction, non-fatal stroke (including ischemic stroke and hemorrhagic stroke) and new renal replacement therapy. RESULTS: The study found that the use of SGLT2 inhibitors or ARNI was associated with a lower risk of ASCVD in patients with coexisting diabetes and heart failure. CONCLUSION: The study suggests that the use of SGLT2 inhibitors, alone or in combination with Entresto, may be effective in reducing the risk of ASCVD and its associated adverse outcomes in patients with diabetes and heart failure. This finding has important implications for the management of these conditions.

Acute mountain sickness on Jade Mountain: Results from the real-world practice (2018-2019).

Acute mountain sickness (AMS) is initiated in response to a hypoxic and hypobaric environment at a high altitude. The precise prevalence of AMS in Jade Mountain climbers remained largely unknown, particularly data obtained from real medical consultations. An overnight stay at the Pai-Yun Lodge (3402 m) is usually required before an ascent of the Jade Mountain. Since 2004, a Pai-Yun Clinic has been established in the Pai-Yun Lodge. The Pai-Yun Clinic provided regular and emergency medical service every weekend. We conducted a retrospective study by using medical records from the Pai-Yun Clinic between 2018 and 2019. A total of 1021 patients were enrolled, with 56.2 % males. Different age groups were 3.2 %, 54.5 %, 37.9 %, and 4.4 % in <20, 20-39, 40-59, and ≥60 years, respectively. There were 582 (57.0 %) patients diagnosed to have AMS (230 [39.5 %] were mild type and 352 [60.5 %] were severe type). The factors associated with AMS development included young age, absence of climbing history (>3000 m) within the last 3 months, first climbing (>3000 m) experience, taking preventive medication, low oxygen saturation, and a high Lake Louise AMS score (LLAMSS). The factors associated with AMS severity included absence of taking preventive medication, low oxygen saturation, and a high LLAMSS. Approximately 15 % of Jade Mountain climbers needed medical service, of which 60 % had AMS. 60 % of patients with AMS must require oxygen supply or medication prescription. Oxygen saturation measure and LLAMSS evaluation are reasonable tools to predict the occurrence and severity of AMS on Jade Mountain.

Effect of acupuncture on ischaemic stroke in patients with rheumatoid arthritis: a nationwide propensity score-matched study.

OBJECTIVE: To demonstrate that acupuncture is beneficial for decreasing the risk of ischaemic stroke in patients with rheumatoid arthritis (RA). DESIGN: A propensity score-matched cohort study. SETTING: A nationwide population-based study. PARTICIPANTS: Patients with RA diagnosed between 1 January 1997 and 31 December 2010, through the National Health Insurance Research Database in Taiwan. INTERVENTIONS: Patients who were administered acupuncture therapy from the initial date of RA diagnosis to 31 December 2010 were included in the acupuncture cohort. Patients who did not receive acupuncture treatment during the same time interval constituted the no-acupuncture cohort. PRIMARY OUTCOME MEASURES: A Cox regression model was used to adjust for age, sex, comorbidities, and types of drugs used. We compared the subhazard ratios (SHRs) of ischaemic stroke between these two cohorts through competing-risks regression models. RESULTS: After 1:1 propensity score matching, a total of 23 226 patients with newly diagnosed RA were equally subgrouped into acupuncture cohort or no-acupuncture cohort according to their use of acupuncture. The basic characteristics of these patients were similar. A lower cumulative incidence of ischaemic stroke was found in the acupuncture cohort (log-rank test, p<0.001; immortal time (period from initial diagnosis of RA to index date) 1065 days; mean number of acupuncture visits 9.83. In the end, 341 patients in the acupuncture cohort (5.95 per 1000 person-years) and 605 patients in the no-acupuncture cohort (12.4 per 1000 person-years) experienced ischaemic stroke (adjusted SHR 0.57, 95% CI 0.50 to 0.65). The advantage of lowering ischaemic stroke incidence through acupuncture therapy in RA patients was independent of sex, age, types of drugs used, and comorbidities. CONCLUSIONS: This study showed the beneficial effect of acupuncture in reducing the incidence of ischaemic stroke in patients with RA.

Associations between femoral 3D curvature and sagittal imbalance of spine.

Background: The sagittal imbalance (SI) of spine triggers compensatory mechanisms (CMs) of lower extremity (LE) to restore trunk balance. These CMs can cause long-period stress on the femur and may possibly alter the femoral morphology. This cross-sectional observational study aimed to answer the following questions: (a) Do SI subjects exhibit greater femoral bowing compared to subjects with sagittal balance? (b) Are there associations between femoral bowing and CMs of LE in SI subjects? Methods: Subjects who underwent biplanar full body radiographs with the EOS imaging system between January 2016 and September 2021 were recruited. Sagittal parameters included T1-pelvic angle (TPA), pelvic incidence (PI), pelvic tilt (PT), sacral slope, lumbar lordosis (LL), PI-LL, and PT/PI ratio. LE parameters were femoral obliquity angle (FOA), knee flexion angle (KA), and ankle dorsiflexion angle. Femoral bowing was quantified as 3D radius of femoral curvature (RFC). Associations between 3D RFC and the radiographic parameters were analyzed. Results: A total of 105 subjects were included, classified into balance group (TPA < 14°, n = 40), SI group (TPA ≥ 14° and KA <5°, n = 30), and SI with knee flexion group (TPA ≥ 14° and KA ≥ 5°, n = 35). 3D RFC was significantly lower in SI with knee flexion group compared to the other two groups (both p < 0.001). Stepwise linear regression showed that age, SI and knee flexion, femoral length (FL), FOA, and KA were independent predictors for 3D RFC. Conclusion: Greater femoral bowing is observed in subjects with SI and knee flexion compared to the balanced population. CM parameters, including KA and FOA, are associated with 3D RFC. Further longitudinal study is needed to investigate the cause-and-effect relationship between SI, CMs of LE, and femoral bowing.

Psychiatric disorders in patients with type 2 diabetes mellitus on sodium-glucose cotransporter-2 inhibitors-a nationwide retrospective cohort study.

To compare the potential role of sodium-glucose cotransporter-2 inhibitors (SGLT2I) in the development of psychiatric disease among patients with type 2 diabetes mellitus (DM). Using a large population-based database, SGLT2I users and non-SGLT2I users were 1:1 matched according to the covariates of sex, age, comorbidities, adapted diabetes complications severity index (DCSI), medications, and index year using propensity score matching and a logistic regression model. We calculated the incidence of major psychiatric disorders and adjusted hazard ratios (HR) with 95% confidence interval (CI) for SGLT2I users and the non- SGLT2I users using a Cox proportional hazards model. SGLT2I were associated with a lower risk for psychiatric disorders than those not treated with SGLT2I (HR 0.80 and 95% CI 0.72-0.88). Among patients with DM, SGLT2I were associated with a lower risk of psychiatric disease.

Sodium-glucose cotransporter-2 inhibitor in risk of sepsis/septic shock among patients with type 2 diabetes mellitus-a retrospective analysis of nationwide medical claims data.

This research is an attempt to investigate the benefit of sodium-glucose cotransporter-2 inhibitor (SGLT2I) use in patients with diabetes mellitus (DM) for outcomes of sepsis/septic shock. We used Taiwan's national data set to identify patients and patients' characteristics to investigate sepsis/septic shock among diabetes patients who use SGLT2I compared to those who do not. We have compared the two groups for several relevant categories of potential risk factors for sepsis/septic shock and adjusted the Cox regression models accordingly. The adapted diabetes complications severity index (DCSI) was used for stratifying the advancing disease of DM. Compared to patients with DCSI = 0, patients with DCSI ≥ 2 had a significantly higher risk of sepsis/septic shock (adjusted HR = 1.52, 95% CI = 1.37-1.68). A significantly lower risk of sepsis/septic shock events was observed in the SGLT2I cohort than in the non-SGLT2I cohort with the DCSI groups [adjusted HR = 0.6 (DCSI group = 0), adjusted HR = 0.61 (DCSI group = 1), adjusted HR = 0.55 (DCSI group ≥ 2)]. Patients who received SGLT2I for a cumulative duration of ≥ 90 days had a significantly lower risk of sepsis/septic shock than patients with a duration of < 90 days (adjusted HR = 0.36, 95% CI = 0.34-0.39). We described a decreased risk of sepsis/septic shock among diabetic patients who took SGLT2I.